Single oncogene expression alters shape and viscoelasticity of breast cancer cells and increases migration

The mechanisms underlying mechanical differences among cancer cell lines with varying metastatic potential are a potential therapeutic target but are not well understood. Although a simple comparison of malignant and benign cell mechanics can reveal differences, these cannot easily be traced back to a specific molecular origin which complicates interpretation. Instead, we asked whether controlled expression of a single oncogene can induce measurable morphological and mechanical changes as well as changes in migration behaviour.

By Atomic Force Microscopy Micro-Rheology on live cell nuclear regions, we demonstrate that controlled expression of the oncogene p95HER2 in breast cancer cells using an antibiotic, is linked to a decreased viscoelastic modulus and a lower transition frequency, suggesting fluidization. The metastatic cells show distinct shape changes and a higher migratory capacity in a pore assay as quantified by deep-learning segmentation. Increased fluidity may aid migration by facilitating passage through endothelial barriers. Our data also show that the mechanical changes are preferentially located in the nucleus whereas a potential remodelling of the surrounding actin cytoskeleton is only minimally related to the viscoelastic changes.